Clinical Scenario:
A 4-month-old infant is brought to the pediatric clinic with poor feeding, generalized weakness, and failure to thrive. Examination reveals marked hypotonia, macroglossia, and cardiomegaly. Echocardiography shows hypertrophic cardiomyopathy. Serum creatine kinase is elevated. Which of the following enzyme deficiencies is responsible for this condition?
A) Acid α-glucosidase deficiency
B) Glucose-6-phosphatase deficiency
C) Lysosomal acid lipase deficiency
D) Muscle phosphorylase deficiency
E) Pyruvate kinase deficiency
Correct answer & Explanation:
Correct Answer:
A) Acid α-glucosidase deficiency
Explanation:
This infant has Pompe disease (Glycogen Storage Disease Type II), an autosomal recessive lysosomal storage disorder caused by deficiency of acid α-glucosidase (acid maltase).
The enzyme normally breaks down glycogen inside lysosomes. Deficiency results in glycogen accumulation, especially in:
- Cardiac muscle → hypertrophic cardiomyopathy
- Skeletal muscle → hypotonia and weakness
- Respiratory muscles → respiratory failure
Why Option A is correct:
Acid α-glucosidase deficiency causes Pompe disease.
Early infantile Pompe disease presents with:
- Hypotonia (“floppy baby”)
- Macroglossia
- Cardiomegaly
- Hypertrophic cardiomyopathy
- Elevated CK
- Feeding difficulty and failure to thrive
Treatment:
- Enzyme replacement therapy (alglucosidase alfa/avalglucosidase alfa)
- Early treatment improves cardiac and motor outcomes
Why other options are incorrect:
B) Glucose-6-phosphatase deficiency
- Causes Von Gierke disease (GSD I): severe fasting hypoglycemia, lactic acidosis, hepatomegaly.
C) Lysosomal acid lipase deficiency
- Causes Wolman disease/Cholesteryl ester storage disease with hepatosplenomegaly and lipid abnormalities.
D) Muscle phosphorylase deficiency
- Causes McArdle disease (GSD V): exercise intolerance and muscle cramps.
E) Pyruvate kinase deficiency
- Causes hemolytic anemia, not glycogen storage disease.
